Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
April-2016 Volume 13 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
April-2016 Volume 13 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Triptolide sensitizes human breast cancer cells to tumor necrosis factor‑α‑induced apoptosis by inhibiting activation of the nuclear factor‑κB pathway

  • Authors:
    • Xiaoli Cheng
    • Wenli Shi
    • Canguo Zhao
    • Dan Zhang
    • Piao Liang
    • Guohui Wang
    • Li Lu
  • View Affiliations / Copyright

    Affiliations: Department of Pathophysiology, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China, Department of Pathology, Guangzhou Nansha Central Hospital, Guangzhou First Municipal People's Hospital, Guangzhou, Guangdong 510180, P.R. China, Department of Internal Medicine, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China
  • Pages: 3257-3264
    |
    Published online on: February 23, 2016
       https://doi.org/10.3892/mmr.2016.4931
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Tumor necrosis factor‑α (TNF‑α) can act as either a tumor promoter, linking inflammation with carcinogenesis, or a tumor inhibitor, inducing cancer cell death. However, several types of cancer, including breast cancer, are resistant to TNF‑α therapy. Triptolide, a diterpene triepoxide, has been reported to exert anti‑inflammatory and antiproliferative effects, associated with the inhibition of nuclear factor‑κB (NF‑κB). The present study investigated the effects of triptolide sensitization on human breast cancer cells to TNF‑α‑induced apoptosis by inhibiting activation of the NF‑κB pathway. Human breast cancer MDA‑MB‑231 cells and MCF‑7 cells were treated with different concentrations of triptolide, with or without 10 ng/ml TNF‑α, for different durations, followed by measurement of cell proliferation using a 3‑[4,5‑dimethyltiazol‑2‑yl]‑2.5‑diphenyl‑tetrazolium bromide assay, apoptosis induction, through determination of caspase‑3 activity and poly (ADP‑ribose) polymerase (PARP) cleavage, and NF‑κB pathway activation, through determination of inhibitor of NF‑κB (IκB) and the NF‑κB downstream genes, X‑linked inhibitor of apoptosis protein (XIAP) and cellular inhibitor of apoptosis protein1/2 (cIAP1/2)] using Western blot and reverse transcription‑quantitative polymerase chain reaction analyses. TNF‑α, when combined with triptolide, was observed to inhibit the activation of IκBα, increase the level of cleaved PARP, and further activate caspase‑3 in the breast cancer cells. Triptolide also inhibited the expression levels of the downstream anti‑apoptotic genes of NF‑κB activation, XIAP and cIAP1/2. The results of the present study demonstrated that triptolide sensitized human breast cancer cells to TNF‑α‑induced apoptosis, which may provide a promising combination strategy for human breast cancer therapeutics.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Labovsky V, Martinez LM, Davies KM, García-Rivello H, Calcagno Mde L, Matas A, Fernández Vallone VB, Wernicke A, Choi H and Chasseing NA: Association between ligands and receptors related to the progression of early breast cancer in tumor epithelial and stromal cells. Clin Breast Cancer. 15:e13–e21. 2015. View Article : Google Scholar

2 

Sung B, Park B, Yadav VR and Aggarwal BB: Celastrol, a triterpene, enhances TRAIL-induced apoptosis through the down-regulation of cell survival proteins and up-regulation of death receptors. J Biol Chem. 285:11498–11507. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Mandal C, Dutta A, Mallick A, Chandra S, Misra L, Sangwan RS and Mandal C: Withaferin A induces apoptosis by activating p38 mitogen-activated protein kinase signaling cascade in leukemic cells of lymphoid and myeloid origin through mitochondrial death cascade. Apoptosis. 13:1450–1464. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Kang DW, Lee JY, Oh DH, Park SY, Woo TM, Kim MK, Park MH, Jang YH and Min do S: Triptolide-induced suppression of phospholipase D expression inhibits proliferation of MDA-MB-231 breast cancer cells. Exp Mol Med. 41:678–685. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Chen BJ: Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb Tripterygium wilfordii Hook F. Leuk Lymphoma. 42:253–265. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Wu WY and Wang YP: Pharmacological actions and therapeutic applications of Salvia miltiorrhiza depside salt and its active components. Acta Pharmacol Sin. 33:1119–1130. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Kiviharju TM, Lecane PS, Sellers RG and Peehl DM: Antiproliferative and proapoptotic activities of triptolide (PG490), a natural product entering clinical trials, on primary cultures of human prostatic epithelial cells. Clin Cancer Res. 8:2666–2674. 2002.PubMed/NCBI

8 

Fidler JM, Li K, Chung C, Wei K, Ross JA, Gao M and Rosen GD: PG490-88, a derivative of triptolide, causes tumor regression and sensitizes tumors to chemotherapy. Mol Cancer Ther. 2:855–862. 2003.PubMed/NCBI

9 

Yang S, Chen J, Guo Z, Xu XM, Wang L, Pei XF, Yang J, Underhill CB and Zhang L: Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther. 2:65–72. 2003.PubMed/NCBI

10 

Tengchaisri T, Chawengkirttikul R, Rachaphaew N, Reutrakul V, Sangsuwan R and Sirisinha S: Antitumor activity of triptolide against cholangiocarcinoma growth in vitro and in hamsters. Cancer Lett. 133:169–175. 1998. View Article : Google Scholar

11 

Liu H, Liu ZH, Chen ZH, Yang JW and Li LS: Triptolide: A potent inhibitor of NF-kappa B in T-lymphocytes. Acta Pharmacol Sin. 21:782–786. 2000.

12 

Lu L, Kanwar J, Schmitt S, Cui QC, Zhang C, Zhao C and Dou QP: Inhibition of tumor cellular proteasome activity by triptolide extracted from the Chinese medicinal plant 'thunder god vineʼ. Anticancer Res. 31:1–10. 2011.PubMed/NCBI

13 

Yang H, Shi G and Dou QP: The tumor proteasome is a primary target for the natural anticancer compound Withaferin A isolated from 'Indian winter cherryʼ. Mol Pharmacol. 71:426–437. 2007. View Article : Google Scholar

14 

Perrone G, Hideshima T, Ikeda H, Okawa Y, Calabrese E, Gorgun G, Santo L, Cirstea D, Raje N, Chauhan D, et al: Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia. 23:1679–1686. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Zhao G, Vaszar LT, Qiu D, Shi L and Kao PN: Anti-inflammatory effects of triptolide in human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 279:L958–L966. 2000.PubMed/NCBI

16 

Sethi G, Ahn KS and Aggarwal BB: Targeting nuclear factor-kappa B activation pathway by thymoquinone: Role in suppression of antiapoptotic gene products and enhancement of apoptosis. Mol Cancer Res. 6:1059–1070. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Eckelman BP, Salvesen GS and Scott FL: Human inhibitor of apoptosis proteins: Why XIAP is the black sheep of the family. Embo Rep. 7:988–994. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Srinivasula SM, Hegde R, Saleh A, Datta P, Shiozaki E, Chai J, Lee RA, Robbins PD, Fernandes-Alnemri T, Shi Y and Alnemri E: A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature. 410:112–116. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Baeuerle PA and Baltimore D: NF-kappa B: Ten years after. Cell. 87:13–20. 1996. View Article : Google Scholar : PubMed/NCBI

20 

Zhao Y, Fu Y, Hu J, Liu Y and Yin X: The effect of tissue factor pathway inhibitor on the expression of monocyte chemotactic protein-3 and IκB-α stimulated by tumour necrosis factor-α in cultured vascular smooth muscle cells. Arch Cardiovasc Dis. 106:4–11. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Gyrd-Hansen M and Meier P: IAPs: From caspase inhibitors to modulators of NF-kappaB, inflammation and cancer. Nat Rev Cancer. 10:561–574. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Takada Y, Singh S and Aggarwal BB: Identification of a p65 peptide that selectively inhibits NF-kappa B activation induced by various inflammatory stimuli and its role in down-regulation of NF-kappaB-mediated gene expression and up-regulation of apoptosis. J Biol Chem. 279:15096–15104. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Vile GF, Tanew-Ilitschew A and Tyrrell RM: Activation of NF-kappa B in human skin fibroblasts by the oxidative stress generated by UVA radiation. Photochem Photobiol. 62:463–468. 1995. View Article : Google Scholar : PubMed/NCBI

24 

Varfolomeev E, Goncharov T, Fedorova AV, Dynek JN, Zobel K, Deshayes K, Fairbrother WJ and Vucic D: c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. J Biol Chem. 283:24295–24299. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Salvesen GS and Duckett CS: IAP proteins: Blocking the road to death's door. Nat Rev Mol Cell Biol. 3:401–410. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Rothe M, Pan MG, Henzel WJ, Ayres TM and Goeddel DV: The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell. 83:1243–1252. 1995. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Cheng X, Shi W, Zhao C, Zhang D, Liang P, Wang G and Lu L: Triptolide sensitizes human breast cancer cells to tumor necrosis factor‑α‑induced apoptosis by inhibiting activation of the nuclear factor‑κB pathway. Mol Med Rep 13: 3257-3264, 2016.
APA
Cheng, X., Shi, W., Zhao, C., Zhang, D., Liang, P., Wang, G., & Lu, L. (2016). Triptolide sensitizes human breast cancer cells to tumor necrosis factor‑α‑induced apoptosis by inhibiting activation of the nuclear factor‑κB pathway. Molecular Medicine Reports, 13, 3257-3264. https://doi.org/10.3892/mmr.2016.4931
MLA
Cheng, X., Shi, W., Zhao, C., Zhang, D., Liang, P., Wang, G., Lu, L."Triptolide sensitizes human breast cancer cells to tumor necrosis factor‑α‑induced apoptosis by inhibiting activation of the nuclear factor‑κB pathway". Molecular Medicine Reports 13.4 (2016): 3257-3264.
Chicago
Cheng, X., Shi, W., Zhao, C., Zhang, D., Liang, P., Wang, G., Lu, L."Triptolide sensitizes human breast cancer cells to tumor necrosis factor‑α‑induced apoptosis by inhibiting activation of the nuclear factor‑κB pathway". Molecular Medicine Reports 13, no. 4 (2016): 3257-3264. https://doi.org/10.3892/mmr.2016.4931
Copy and paste a formatted citation
x
Spandidos Publications style
Cheng X, Shi W, Zhao C, Zhang D, Liang P, Wang G and Lu L: Triptolide sensitizes human breast cancer cells to tumor necrosis factor‑α‑induced apoptosis by inhibiting activation of the nuclear factor‑κB pathway. Mol Med Rep 13: 3257-3264, 2016.
APA
Cheng, X., Shi, W., Zhao, C., Zhang, D., Liang, P., Wang, G., & Lu, L. (2016). Triptolide sensitizes human breast cancer cells to tumor necrosis factor‑α‑induced apoptosis by inhibiting activation of the nuclear factor‑κB pathway. Molecular Medicine Reports, 13, 3257-3264. https://doi.org/10.3892/mmr.2016.4931
MLA
Cheng, X., Shi, W., Zhao, C., Zhang, D., Liang, P., Wang, G., Lu, L."Triptolide sensitizes human breast cancer cells to tumor necrosis factor‑α‑induced apoptosis by inhibiting activation of the nuclear factor‑κB pathway". Molecular Medicine Reports 13.4 (2016): 3257-3264.
Chicago
Cheng, X., Shi, W., Zhao, C., Zhang, D., Liang, P., Wang, G., Lu, L."Triptolide sensitizes human breast cancer cells to tumor necrosis factor‑α‑induced apoptosis by inhibiting activation of the nuclear factor‑κB pathway". Molecular Medicine Reports 13, no. 4 (2016): 3257-3264. https://doi.org/10.3892/mmr.2016.4931
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team